The initiation of an immune response against a specific antigen in mammals is brought about by presentation of that antigen to T-cells. An antigen is presented to T cells in the context of a major histocompatibility complex (MHC). MHCs are located on the surface of antigen presenting cells (APCs); the three-dimensional structure of MHCs includes a groove or cleft into which the presented antigen fits. When an appropriate receptor on a T-cell interacts with the MHC/antigen complex on an APC in the presence of necessary co-stimulatory signals, the T-cell is stimulated, triggering various aspects of the well-characterized cascade of immune system activation events, including induction of cytotoxic T-cell function, induction of B-cell function, and stimulation of cytokine production.
The pathology of multiple sclerosis is characterized by an abnormal immune response directed against the central nervous system. In particular, T-lymphocytes reactive against myelin antigens are believed to initiate an inflammatory response within the central nervous system. The resultant inflammatory response includes recruited T-lymphocytes, activated macrophages, B-lymphocytes and plasma cells. Soluble mediators released by these inflammatory cells result in demyelination and axonal degeneration. Similarly, inflammatory responses in many autoimmune disorders result in tissue damage, often of a progressive nature. Despite recent progress, effective treatments of autoimmune and inflammatory disorders are still needed.
Major histocompatibility complex (MHC) class II α1 domain polypeptides have proven useful in treatment of multiple sclerosis (WO 2013/103816, which is incorporated by reference herein).